We propose to continue our investigation of the mouse mammary tumor virus (MMTV) and its relationship to the development of mammary cancer in mice. We will apply a wide variety of molecular techniques (including nucleic acid hybridization and biochemical procedures for determining size and structure of nucleic acids) to a large number of biological reagents, including several virus strains propagated in vivo and in vitro, mouse strains with high and low incidence of mammary tumors, normal tissues and tumors from these mice, cultured mammary tumor cells, human mammary tumors, etc. Our central goals include characterization of: (1) the genome of MMTV (its complexity, homology among several strains, association with low molecular weight RNAs); (2) the putative RNA primer for viral DNA synthesis; (3) the MMTV-specific DNA present in normal cells from high and low incidence strains; (4) the activity of MMTV as an infectious agent in vivo and in culture; (5) the metabolism of viral RNA in cultured cells; (6) the mechanism of regulation of MMTV gene expression by glucocorticoid hormones; and (7) the relationship, if any, of MMTV to human mammary cancer.